EFFECTIVENESS AND TOXICITY SCREENING OF VARIOUS ABSORPTION ENHANCERS IN THE RAT SMALL-INTESTINE - EFFECTS OF ABSORPTION ENHANCERS ON THE INTESTINAL-ABSORPTION OF PHENOL RED AND THE RELEASE OF PROTEIN AND PHOSPHOLIPIDS FROM THE INTESTINAL-MEMBRANE

Sodium glycocholate, sodium taurocholate, sodium deoxycholate, EDTA, s odium salicylate, sodium caprate, diethyl maleate, N-lauryl-beta-D-mal topyranoside, linoleic acid polyoxyethylated (60 mol) mixed micelles ( all 20 mM) have been ranked in order of their effectiveness as enhance rs of the absorption of drugs in the rat small intestine, by use of an in-situ loop model with phenol red as a model drug. Local toxicity in rats was examined by assessing protein and phospholipid release as bi ological markers. Of the absorption enhancers, sodium deoxycholate, ED TA and N-lauryl-beta-D-maltopyranoside were the most effective; sodium deoxycholate and EDTA, however, caused significant release of protein and phospholipids. N-lauryl-beta-D-maltopyranoside, on the other hand , did not damage the small intestinal membrane. Sodium taurocholate en hanced phenol red absorption from the small intestine and resulted in little or no protein and phospholipids release. Sodium salicylate, die thyl maleate and the mixed micelles had no absorption-promoting effect s on phenol red. There was good correlation between the area under the plasma concentration-time curve for phenol red and the amounts of pro tein and phospholipid released in the presence of absorption enhancers . From these results it might be concluded that N-lauryl-beta-D-maltop yranoside and sodium taurocholate are effective absorption enhancers w hich have low toxicity levels at a concentration of 20 mM.